The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration

被引:158
作者
Cieslewicz, G
Tomkinson, A
Adler, A
Duez, C
Schwarze, J
Takeda, K
Larson, KA
Lee, JJ
Irvin, CG
Gelfand, EW
机构
[1] Natl Jewish Med & Res Ctr, Dept Pediat, Div Basic Sci, Denver, CO 80206 USA
[2] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA
[3] Mayo Clin Scottsdale, Dept Biochem & Mol Biol, Scottsdale, AZ 85259 USA
关键词
D O I
10.1172/JCI7010
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5-30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti-IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.
引用
收藏
页码:301 / 308
页数:8
相关论文
共 24 条
[11]   Requirement for CD8(+) T cells in the development of airway hyperresponsiveness in a murine model of airway sensitization [J].
Hamelmann, E ;
Oshiba, A ;
Paluh, J ;
Bradley, K ;
Loader, J ;
Potter, TA ;
Larsen, GL ;
Gelfand, EW .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (04) :1719-1729
[12]   Antiinterleukin-5 antibody prevents airway hyperresponsiveness in a murine model of airway sensitization [J].
Hamelmann, E ;
Oshiba, A ;
Loader, J ;
Larsen, GL ;
Gleich, G ;
Lee, J ;
Gelfand, EW .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 155 (03) :819-825
[13]   Development of airway hyperresponsiveness is dependent on interferon-gamma and independent of eosinophil infiltration [J].
Hessel, EM ;
VanOosterhout, AJM ;
VanArk, I ;
VanEsch, B ;
Hofman, G ;
VanLoveren, H ;
Savelkoul, HFJ ;
Nijkamp, FP .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1997, 16 (03) :325-334
[14]  
HESSEL EM, 1995, EUR J PHARM-ENVIRON, V293, P401, DOI 10.1016/S0014-2999(95)80099-9
[15]   THE EFFECT OF CROMOLYN SODIUM AND ALBUTEROL ON EARLY AND LATE PHASE BRONCHOCONSTRICTION AND AIRWAY LEUKOCYTE INFILTRATION AFTER ALLERGEN CHALLENGE OF NONANESTHETIZED GUINEA-PIGS [J].
HUTSON, PA ;
HOLGATE, ST ;
CHURCH, MK .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1988, 138 (05) :1157-1163
[16]   EARLY AND LATE-PHASE BRONCHOCONSTRICTION AFTER ALLERGEN CHALLENGE OF NONANESTHETIZED GUINEA-PIGS .1. THE ASSOCIATION OF DISORDERED AIRWAY PHYSIOLOGY TO LEUKOCYTE INFILTRATION [J].
HUTSON, PA ;
CHURCH, MK ;
CLAY, TP ;
MILLER, P ;
HOLGATE, ST .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1988, 137 (03) :548-557
[17]   EXPERIMENTAL ASTHMA IN GUINEA-PIGS REVISITED [J].
KALLOS, P ;
KALLOS, L .
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 1984, 73 (01) :77-85
[18]  
MARSH WR, 1985, AM REV RESPIR DIS, V131, P875
[19]  
METZGER WJ, 1987, AM REV RESPIR DIS, V135, P433
[20]  
MURPHY KR, 1986, AM REV RESPIR DIS, V134, P62